The relationship between dietary fat and mammary carcinogenesis was examined by feeding a high fat/low carbohydrate (HF) or a low fat/high carbohydrate (LF) diet to rats receiving a dose of N-methylnitrosurea. Rats on a HF diet invariably developed mammary tumors earlier and in higher incidence than their counterparts on a LF diet. A threshold dose of NMU was capable of inducing mammary tumors in rats on a HF diet but not in rats on a LF diet. By changing the diet from a HF to a LF diet-or from a LF to a HF diet at different times after NMU treatment, it was found that a HF diet exerted its effect both at the initiation and the promotional phase of carcinogenesis. Autoradiographic analyses indicated that a HF diet elevated the 3H-thymidine incorporative rate of mammary cells at the prepubertal, pubertal and adult period. The increased cell proliferative activity may account for the cocarcinogenic effect of a HF diet. Further studies are underway to identify the type and amount of fat (fatty acid) that may be responsible for the enhancement of mammary carcinogenesis and to determine whether the effect may be exerted directly on the mammary cells or indirectly via the endocrine system.